Missed Diagnoses and Health Problems in Adults With Prader-Willi Syndrome: Recommendations for Screening and Treatment

Abstract

Context: Prader-Willi syndrome (PWS) is a complex hypothalamic disorder, combining hyperphagia, hypotonia, intellectual disability, and pituitary hormone deficiencies. Annual mortality of patients with PWS is high (3%). In half of the patients, the cause of death is obesity related and/or of cardiopulmonary origin. Health problems leading to this increased mortality often remain undetected due to the complexity and rareness of the syndrome.

Objective: To assess the prevalence of health problems in adults with PWS retrospectively.

Patients, design, and setting: We systematically screened 115 PWS adults for undiagnosed health problems. All patients visited the multidisciplinary outpatient clinic for rare endocrine syndromes at the Erasmus University Medical Center, Rotterdam, Netherlands. We collected the results of medical questionnaires, interviews, physical examinations, biochemical measurements, polygraphy, polysomnography, and radiology.

Main outcome measures: Presence or absence of endocrine and nonendocrine comorbidities in relation to living situation, body mass index, genotype, and demographic factors.

Results: Seventy patients (61%) had undiagnosed health problems, while 1 in every 4 patients had multiple undiagnosed health problems simultaneously. All males and 93% of females had hypogonadism, 74% had scoliosis, 18% had hypertension, 19% had hypercholesterolemia, 17% had type 2 diabetes mellitus, and 17% had hypothyroidism. Unfavorable lifestyles were common: 22% exercised too little (according to PWS criteria) and 37% did not see a dietitian.

Conclusions: Systematic screening revealed many undiagnosed health problems in PWS adults. Based on patient characteristics, we provide an algorithm for diagnostics and treatment, with the aim to prevent early complications and reduce mortality in this vulnerable patient group.

Keywords: Prader-Willi syndrome; cardiovascular system; comorbidity; failure to rescue; health care; missed diagnosis.

Figure 1.

Factors contributing to cardiopulmonary disease in patients with PWS. Abbreviations: BMR, basal metabolic rate; diet ,dietitian; endo, endocrinologist; ID, physician for people with intellectual disabilities; LBM, lean body mass; OAHS, obesity associated hypoventilation syndrome; physio, physiotherapist; PWS, Prader-Willi syndrome; psych, psychologist. Legend: black arrows indicate a cause-and-effect relationship; dotted lines indicate an intervention; the stands for an intervention with medication; black borders indicate that the factor is inherent to the syndrome; dotted black border indicates that the factor is inherent to the syndrome, but can be aggravated by cardiopulmonary disease (12–39).

Figure 2.

Health problems detected by systematic health screening in 115 adults with PWS. Abbreviation: PWS, Prader-Willi syndrome. Legend: black bars indicate the percentage of health problems already diagnosed before the screening; gray bars indicate the percentage of health problems that were revealed by screening.

Figure 3.

Algorithm for diagnostics and treatment in adults with PWS. Abbreviations: BMI, body mass index; DEXA, dual energy X-ray absorptiometry; FSH, follicle-stimulating hormone; FT4, free thyroxin; HbA1c, hemoglobin A1c; ITT, insulin tolerance test; LDL, low density lipoprotein; LH, luteinizing hormone; MTP, metyrapone test; PWS, Prader-Willi syndrome; SHBG, sex hormone binding globulin. ^aRecommendation based on expert opinion and literature review (65–67). ^bBased on previously published data (68).